Models of hybridization during range expansions and their application to recent human evolution

Several lines of genetic, archeological and paleontological evidence suggest that anatomically modern humans (Homo sapiens) colonized the world in the last 60,000 years by a series of migrations originating from Africa (e.g. Liu et al., 2006; Handley et al., 2007; Prugnolle, Manica, and Balloux, 2005; Ramachandran et al. 2005; Li et al. 2008; Deshpande et al. 2009; Mellars, 2006a, b; Lahr and Foley, 1998; Gravel et al., 2011; Rasmussen et al., 2011). With the progress of ancient DNA analysis, it has been shown that archaic humans hybridized with modern humans outside Africa. Recent direct analyses of fossil nuclear DNA have revealed that 1–4 percent of the genome of Eurasian has been likely introgressed by Neanderthal genes (Green et al., 2010; Reich et al., 2010; Vernot and Akey, 2014; Sankararaman et al., 2014; Prufer et al., 2014; Wall et al., 2013), with Papua New Guineans and Australians showing even larger levels of admixture with Denisovans (Reich et al., 2010; Skoglund and Jakobsson, 2011; Reich et al., 2011; Rasmussen et al., 2011). It thus appears that the past history of our species has been more complex than previously anticipated (Alves et al., 2012), and that modern humans hybridized several times with local hominins during their expansion out of Africa, but the exact mode, time and location of these hybridizations remain to be clarifi ed (Ibid.; Wall et al., 2013). In this context, we review here a general model of admixture during range expansion, which lead to some predictions about expected patterns of introgression that are relevant to modern human evolution.

Determination of vertebral range of motion using inertial measurement units in 27 Franches-Montagnes stallions and comparison between conditions and with a mixed population

REASONS FOR PERFORMING STUDY: The diagnosis of equine back disorders is challenging. Objectively determining movement of the vertebral column may therefore be of value in a clinical setting. OBJECTIVES: To establish whether surface-mounted inertial measurement units (IMUs) can be used to establish normal values for range of motion (ROM) of the vertebral column in a uniform population of horses trotting under different conditions. STUDY DESIGN: Vertebral ROM was established in Franches-Montagnes stallions and a general population of horses and the variability in measurements compared between the two groups. Repeatability and the influence of specific exercise condition (on ROM) were assessed. Finally, attempts were made to explain the findings of the study through the evaluation of factors that might influence ROM. METHODS: Dorsoventral (DV) and mediolateral (ML) vertebral ROM was measured at a trot under different exercise conditions in 27 Franches-Montagnes stallions and six general population horses using IMUs distributed over the vertebral column. RESULTS: Variability in the ROM measurements was significantly higher for general population horses than for Franches-Montagnes stallions (both DV and ML ROM). Repeatability was strong to very strong for DV measurements and moderate for ML measurements. Trotting under saddle significantly reduced the ROM, with sitting trot resulting in a significantly lower ROM than rising trot. Age is unlikely to explain the low variability in vertebral ROM recorded in the Franches-Montagnes horses, while this may be associated with conformational factors. CONCLUSIONS: It was possible to establish a normal vertebral ROM for a group of Franches-Montagnes stallions. While within-breed variation was low in this population, further studies are necessary to determine variation in vertebral ROM for other breeds and to assess their utility for diagnosis of equine back disorders.

Towards clinical computed ultrasound tomography in echo-mode: Dynamic range artefact reduction

Computed ultrasound tomography in echo-mode (CUTE) allows imaging the speed of sound inside tissue using hand-held pulse-echo ultrasound. This technique is based on measuring the changing local phase of beamformed echoes when changing the transmit beam steering angle. Phantom results have shown a spatial resolution and contrast that could qualify CUTE as a promising novel diagnostic modality in combination with B-mode ultrasound. Unfortunately, the large intensity range of several tens of dB that is encountered in clinical images poses difficulties to echo phase tracking and results in severe artefacts. In this paper we propose a modification to the original technique by which more robust echo tracking can be achieved, and we demonstrate in phantom experiments that dynamic range artefacts are largely eliminated. Dynamic range artefact reduction also allowed for the first time a clinical implementation of CUTE with sufficient contrast to reproducibly distinguish the different speed of sound in different tissue layers of the abdominal wall and the neck.

Range of Motion of the Upper Extremity in a Healthy Pediatric Population: Introduction to Normative Data.

Objective In the pediatric population traumatic injuries of the upper extremity are common. After therapy a decision has to be made if the mobility of the joint lies within a normal range. The purpose of this study was to give an introduction to normative data. We investigate if there is a significant difference in the range of motion (ROM) between male and female probands and furthermore, if an effect of the age can be detected. Methods We performed an institutional review board-approved study of healthy girls and boys aged between 2 and 16 years without any medical history of an upper extremity fracture. We investigated the active ROM of the elbow, wrist, metacarpophalangeal, and interphalangeal joints. Furthermore, age, handedness, weight, and height were recorded. A total of 171 adolescents with a mean age of 10.6 years were included and separated into four cohorts by age: 2 to 5, 6 to 10, 11 to 13, and 14 to 16 years. Results We found significant differences between the genders in the age group from 11 to 13 years for the flexion of the elbow, the pronation, the flexion of the interphalangeal joint of the thumb, as well as the flexion of the metacarpophalangeal joints of digitus II to V. Furthermore, a significant difference in the same joints except from the elbow flexion could be demonstrated between the genders. Conclusion Our study contributes normative data for upper extremity ROM in the pediatric population and presents a gender-related difference in certain joints. Clinical Relevance Normative data for the ROM of upper extremity joints in children is helpful for the evaluation of pediatric orthopedic patients and provides the framework for therapeutic resolution. Since a great number of traumatic injuries in children affect the upper extremity, this information may help the physician to estimate the impact of the injury and decide on the therapeutic management.

TIMS measurements of full range of natural Ca isotopes with internally consistent fractionation correction

This study presents static measurements of the Ca isotopic composition of standard reference materials SRM 915 a/b on a Triton Plus™ thermal ionization mass spectrometer with a specially developed Faraday cup array allowing simultaneous measurement of 40Ca and 48Ca. The total amount of Ca in all analyses was kept < 1 µg. With this setup the measurement uncertainties were 0.06 ‰ for 40Ca/44Ca and 0.12 ‰ for 48Ca/40Ca. Measuring all isotopes simultaneously better allows to test the internal consistency of different Ca isotope abundances reported in the literature. The exponential law was observed to correct incompletely instrumental mass fractionation. An improved fractionation correction based on the exponential law is proposed. It changes the 40Ca/44Ca ratio of SRM 915a (corrected relative to 42Ca/44Ca = 0.31221; 48Ca/44Ca = 0.08871) from 47.1635 ± 0.0028 to 47.1649 ± 0.0047. The measurements of SRM 915b were performed with different analytical conditions (runs were prolonged till complete filament load depletion). Even if the 40Ca/44Ca ratio of SRM 915b, when corrected with the simple exponential law, appears different (47.1532 ± 0.0038) from that of SRM 915a, it becomes coincident (47.1613 ± 0.0028) when corrected with a second-order refinement. This supports the use of the improved exponential law to obtain internally consistent Ca isotope ratio for natural samples.

Periacetabular osteotomy restores the typically excessive range of motion in dysplastic hips with a spherical head

BACKGROUND Residual acetabular dysplasia is seen in combination with femoral pathomorphologies including an aspherical femoral head and valgus neck-shaft angle with high antetorsion. It is unclear how these femoral pathomorphologies affect range of motion (ROM) and impingement zones after periacetabular osteotomy. QUESTIONS/PURPOSES (1) Does periacetabular osteotomy (PAO) restore the typically excessive ROM in dysplastic hips compared with normal hips; (2) how do impingement locations differ in dysplastic hips before and after PAO compared with normal hips; (3) does a concomitant cam-type morphology adversely affect internal rotation; and (4) does a concomitant varus-derotation intertrochanteric osteotomy (IO) affect external rotation? METHODS Between January 1999 and March 2002, we performed 200 PAOs for dysplasia; of those, 27 hips (14%) met prespecified study inclusion criteria, including availability of a pre- and postoperative CT scan that included the hip and the distal femur. In general, we obtained those scans to evaluate the pre- and postoperative acetabular and femoral morphology, the degree of acetabular reorientation, and healing of the osteotomies. Three-dimensional surface models based on CT scans of 27 hips before and after PAO and 19 normal hips were created. Normal hips were obtained from a population of CT-based computer-assisted THAs using the contralateral hip after exclusion of symptomatic hips or hips with abnormal radiographic anatomy. Using validated and computerized methods, we then determined ROM (flexion/extension, internal- [IR]/external rotation [ER], adduction/abduction) and two motion patterns including the anterior (IR in flexion) and posterior (ER in extension) impingement tests. The computed impingement locations were assigned to anatomical locations of the pelvis and the femur. ROM was calculated separately for hips with (n = 13) and without (n = 14) a cam-type morphology and PAOs with (n = 9) and without (n = 18) a concomitant IO. A post hoc power analysis based on the primary research question with an alpha of 0.05 and a beta error of 0.20 revealed a minimal detectable difference of 4.6° of flexion. RESULTS After PAO, flexion, IR, and adduction/abduction did not differ from the nondysplastic control hips with the numbers available (p ranging from 0.061 to 0.867). Extension was decreased (19° ± 15°; range, -18° to 30° versus 28° ± 3°; range, 19°-30°; p = 0.017) and ER in 0° flexion was increased (25° ± 18°; range, -10° to 41° versus 38° ± 7°; range, 17°-41°; p = 0.002). Dysplastic hips had a higher prevalence of extraarticular impingement at the anteroinferior iliac spine compared with normal hips (48% [13 of 27 hips] versus 5% [one of 19 hips], p = 0.002). A PAO increased the prevalence of impingement for the femoral head from 30% (eight of 27 hips) preoperatively to 59% (16 of 27 hips) postoperatively (p = 0.027). IR in flexion was decreased in hips with a cam-type deformity compared with those with a spherical femoral head (p values from 0.002 to 0.047 for 95°-120° of flexion). A concomitant IO led to a normalization of ER in extension (eg, 37° ± 7° [range, 21°-41°] of ER in 0° of flexion in hips with concomitant IO compared with 38° ± 7° [range, 17°-41°] in nondysplastic control hips; p = 0.777). CONCLUSIONS Using computer simulation of hip ROM, we could show that the PAO has the potential to restore the typically excessive ROM in dysplastic hips. However, a PAO can increase the prevalence of secondary intraarticular impingement of the aspherical femoral head and extraarticular impingement of the anteroinferior iliac spines in flexion and internal rotation. A cam-type morphology can result in anterior impingement with restriction of IR. Additionally, a valgus hip with high antetorsion can result in posterior impingement with decreased ER in extension, which can be normalized with a varus derotation IO of the femur. However, indication of an additional IO needs to be weighed against its inherent morbidity and possible complications. The results are based on a limited number of hips with a pre- and postoperative CT scan after PAO. Future prospective studies are needed to verify the current results based on computer simulation and to test their clinical importance.

Thyroid function within the normal range and risk of coronary heart disease: an individual participant data analysis of 14 cohorts

IMPORTANCE Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD). OBJECTIVE To assess the association between differences in thyroid function within the reference range and CHD risk. DESIGN, SETTING, AND PARTICIPANTS Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55,412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline. EXPOSURES Thyroid function as expressed by serum thyrotropin levels at baseline. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status. RESULTS Among 55,412 individuals, 1813 people (3.3%) died of CHD during 643,183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48,875 individuals (9.5%) experienced a first-time CHD event during 533,408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results. CONCLUSIONS AND RELEVANCE Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.

Visual-auditory differences in duration discrimination of intervals in the subsecond and second range

A common finding in time psychophysics is that temporal acuity is much better for auditory than for visual stimuli. The present study aimed to examine modality-specific differences in duration discrimination within the conceptual framework of the Distinct Timing Hypothesis. This theoretical account proposes that durations in the lower milliseconds range are processed automatically while longer durations are processed by a cognitive mechanism. A sample of 46 participants performed two auditory and visual duration discrimination tasks with extremely brief (50-ms standard duration) and longer (1000-ms standard duration) intervals. Better discrimination performance for auditory compared to visual intervals could be established for extremely brief and longer intervals. However, when performance on duration discrimination of longer intervals in the 1-s range was controlled for modality-specific input from the sensory-automatic timing mechanism, the visual-auditory difference disappeared completely as indicated by virtually identical Weber fractions for both sensory modalities. These findings support the idea of a sensory-automatic mechanism underlying the observed visual-auditory differences in duration discrimination of extremely brief intervals in the millisecond range and longer intervals in the 1-s range. Our data are consistent with the notion of a gradual transition from a purely modality-specific, sensory-automatic to a more cognitive, amodal timing mechanism. Within this transition zone, both mechanisms appear to operate simultaneously but the influence of the sensory-automatic timing mechanism is expected to continuously decrease with increasing interval duration.

A ~ 32-70 K formation temperature range for the ice grains agglomerated by Comet 67P/Churyumov-Gerasimenko

Grand Canonical Monte Carlo simulations are used to reproduce the N₂/CO ratio ranging between 1.7 x 10⁻³ and 1.6 x 10⁻² observed in situ in the Jupiter-family comet 67 P/Churyumov-Gerasimenko (67 P) by the ROSINA mass spectrometer on board the Rosetta spacecraft. By assuming that this body has been agglomerated from clathrates in the protosolar nebula (PSN), simulations are developed using elaborated interatomic potentials for investigating the temperature dependence of the trapping within a multiple-guest clathrate formed from a gas mixture of CO and N₂ in proportions corresponding to those expected for the PSN. By assuming that 67 P agglomerated from clathrates, our calculations suggest the cometary grains must have been formed at temperatures ranging between ~ 31.8 and 69.9 K in the PSN to match the N₂/CO ratio measured by the ROSINA mass spectrometer. The presence of clathrates in Jupiter-family comets could then explain the potential N₂ depletion (factor of up to ~ 87 compared to the protosolar value) measured in 67 P/Churyumov-Gerasimenko.

Detection efficiency of microchannel plates for e(-) and pi(-) in the momentum range from 17.5 to 345 MeV/c

High-energy e(-) and pi(-) were measured by the multichannel plate (MCP) detector at the PiM1 beam line of the High Intensity Proton Accelerator Facilities located at the Paul Scherrer Institute, Villigen, Switzerland. The measurements provide the absolute detection efficiencies for these particles: 5.8% +/- 0.5% for electrons in the beam momenta range 17.5-300 MeV/c and 6.0% +/- 1.3% for pions in the beam momenta range 172-345 MeV/c. The pulse height distribution determined from the measurements is close to an exponential function with negative exponent, indicating that the particles penetrated the MCP material before producing the signal somewhere inside the channel. Low charge extraction and nominal gains of the MCP detector observed in this study are consistent with the proposed mechanism of the signal formation by penetrating radiation. A very similar MCP ion detector will be used in the Neutral Ion Mass (NIM) spectrometer designed for the JUICE mission of European Space Agency (ESA) to the Jupiter system, to perform measurements of the chemical composition of the Galilean moon exospheres. The detection efficiency for penetrating radiation determined in the present studies is important for the optimisation of the radiation shielding of the NIM detector against the high-rate and high-energy electrons trapped in Jupiter's magnetic field. Furthermore, the current studies indicate that MCP detectors can be useful to measure high-energy particle beams at high temporal resolution. (C) 2015 AIP Publishing LLC.